Skeletal muscle atrophy is an inevitable consequence of growing old. Age-related muscle atrophy is associated with a significant decline in protein synthesis but little is known of the cellular mechanisms by which anabolic activity is reduced in aging skeletal muscle. One possibility is that the total quantity of genetic material available for synthetic activity is reduced. In other words, there may be a loss of myonuclei with age. A loss in myonuclei could reduce overall rates of transcription and ultimately, protein synthesis. As a result, muscle fiber atrophy may ensue. The proposed research will examine the relationship between myonuclear population dynamics and myofiber atrophy. It is hypothesized that the balance between myonuclear loss and myonuclear accretion is disrupted in aging skeletal muscle resulting in a loss of myofiber nuclei. To test this hypothesis, the effect of age on myonuclear degeneration, accretion and population size in muscles that show age-related atrophy (soleus and plantaris) and muscles that do not (flexor digitorum longus (FL) and adductor longus (AL). In addition, the effect of exercise training on myonuclear population size, accretion and loss will be examined. It is reasoned that if muscle atrophy is due to an imbalance in myonuclear loss and accretion, then exercise training, an intervention shown to preserve muscle mass, should restore this balance. Adult (six months old), middle-aged (twelve months old) and old (twenty-four months old) Fischer 344 male rats will be assigned to an exercise trained or sedentary control group. Following ten weeks of run training, the size of the myonuclear population will be estimated by morphometric measurements. In situ and biochemical assays for DNA fragmentation will be used to quantitate the incidence of myonuclear degeneration. Myonuclear accretion will be assessed by labeling all nuclei formed during the last week of the study with 5-bromo-2-deoxyuridine (BrdU), a thymidine analog. The proposed research is a first step toward identifying cellular mechanisms that play a role in age-related muscle atrophy. Understanding these mechanisms is imperative for developing strategies to prevent and counteract this process.
